Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression

Woosuk Chung; Su Yeon Choi; Eunee Lee; Haram Park; Jaeseung Kang; Hanwool Park; Yeonsoo Choi; Dongsoo Lee; Sae Geun Park; Ryunhee Kim; Yi Sul Cho; Jeonghoon Choi; Myoung Hwan Kim; Jong Won Lee; Seungjoon Lee; Issac Rhim; Min Whan Jung; Daesoo Kim; Yong Chul Bae; Eunjoon Kim

doi:10.1038/nn.3927

Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression

Woosuk Chung, Su Yeon Choi, Eunee Lee, Haram Park, Jaeseung Kang, Hanwool Park, Yeonsoo Choi, Dongsoo Lee, Sae Geun Park, Ryunhee Kim, Yi Sul Cho, Jeonghoon Choi, Myoung Hwan Kim, Jong Won Lee, Seungjoon Lee, Issac Rhim, Min Whan Jung, Daesoo Kim, Yong Chul Bae, Eunjoon Kim

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133 Scopus citations

Abstract

Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53 ^-/- mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.

Original language	English
Pages (from-to)	435-446
Number of pages	12
Journal	Nature Neuroscience
Volume	18
Issue number	3
DOIs	https://doi.org/10.1038/nn.3927
State	Published - 27 Mar 2015

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title = "Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression",

abstract = "Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53 -/- mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.",

author = "Woosuk Chung and Choi, {Su Yeon} and Eunee Lee and Haram Park and Jaeseung Kang and Hanwool Park and Yeonsoo Choi and Dongsoo Lee and Park, {Sae Geun} and Ryunhee Kim and Cho, {Yi Sul} and Jeonghoon Choi and Kim, {Myoung Hwan} and Lee, {Jong Won} and Seungjoon Lee and Issac Rhim and Jung, {Min Whan} and Daesoo Kim and Bae, {Yong Chul} and Eunjoon Kim",

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AU - Chung, Woosuk

AU - Choi, Su Yeon

AU - Lee, Eunee

AU - Park, Haram

AU - Kang, Jaeseung

AU - Park, Hanwool

AU - Choi, Yeonsoo

AU - Lee, Dongsoo

AU - Park, Sae Geun

AU - Kim, Ryunhee

AU - Cho, Yi Sul

AU - Choi, Jeonghoon

AU - Kim, Myoung Hwan

AU - Lee, Jong Won

AU - Lee, Seungjoon

AU - Rhim, Issac

AU - Jung, Min Whan

AU - Kim, Daesoo

AU - Bae, Yong Chul

AU - Kim, Eunjoon

PY - 2015/3/27

Y1 - 2015/3/27

N2 - Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53 -/- mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.

AB - Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53 -/- mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.

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Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression

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